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Harmala and Essential Tremor (and Parkinsons)

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mmcakes

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I smoked my fair share of changa over this past summer (quite a bit, most days) and I've had a persistent essential tremor that I've noticed since October. Apparently there is a causative link between harmaline consumption and this neurological issue, which is unfortunate (had I known this at the time I would probably not have smoked this). There is also a potential link to Parkinsons, which I really hope I don't get in the future. Apparently the beta carbolines (harmaline in particular) are fat soluble and accumulate in brain tissue.


I'm curious if any other harmala users (heavy users) have noted this occurrence and if anyone has identified a solution or a way to detoxify this chemicals from the brain. It's really unfortunate that I have this now, even though it's relatively mild - I use my hands for work and play guitar etc. Even typing on my phone is fairly difficult and the tremors are exacerbated by various stressors which sometimes makes them unmanageable. I really hope to find a solution and want to warn others.



sources:
link.springer.com

Elevated levels of harman and norharman in cerebrospinal fluid of Parkinsonian patients - Journal of Neural Transmission

Death of dopaminergic neurons in Parkinson's disease (PD) may partially be caused by synthesis and accumulation of endogenous and exogenous toxins. Because of structural similarity to MPTP, β-carbolines, like norharman and harman, have been proposed as putative neurotoxins. In vivo they may...
link.springer.com link.springer.com


Can anyone comment on this? I'm surprised there is so little discussion regarding this potential danger with harmala use. I only found one thread tangentially discussing this.
 
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I always noticed an essential tremor when using harmalas from rue, but it's gone away since I stopped daily use.

The articles you cite talk about harman (aka harmane) and norharman. Harman is present in rue, but it is also present in coffee and cigarettes.

According to this, coffee can contain 210 ug of harman per liter. According to wikipedia, rue contains .16% harman. So if my math is right that is 1600 ug of harman per gram of rue. That is a lot more than in coffee, but people who drink coffee daily probably end up consuming more harman than people who use rue occasionally. And I can't find anything about coffee causing Parkinson's. In fact a quick google search came up with many articles saying that coffee could decrease risk of Parkinson's.

It doesn't look like caapi has any significant amount of harman in it.

I couldn't find anything about rue or caapi containing norharman either.

So I wouldn't worry too much about the harman and norharman content of your changa. I also don't know, if you manske your rue extract whether or not that gets rid of that stuff in the product.

As for harmine and harmaline, according to this:
The endogenous harmala alkaloids have been proven to be involved in Parkinson's disease.[31] One study on both endogenous and exogenous beta-carbolines showed that they all have general DAT-mediated (Dopamine active transporter-mediated) dopaminergic toxicity and therefore, are involved in the pathogenesis of Parkinson's disease.[36] Adversely, it was revealed in an in vitro study that two of these endogenous compounds, norharman and 9-methylnorharman, have good anti-parkinsonism effects via inhibition of MAO-B, an enzyme involved in the production of parkinsonism-related substances from the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. However, naturally occurring beta-carbolines had almost no such inhibitory effect.[33]

In contrast, several studies on the anti-parkinsonism effect of B. caapi revealed that its beta-carboline content (harmine and harmaline) has significant effect against this disease through the inhibition of MAO-B.[37,38] Although, these beta-carbolines with anti-parkinsonism effect are also present in P. harmala, there have been no studies conducted regarding the possible effect of P. harmala isolated alkaloids against Parkinson's disease, thus far.
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So I don't quite know what this means, although it looks pretty ambiguous - the alkaloids could contribute to Parkinson's disease, but they can also treat it.

This article specifically says that the acute tremor caused by harmaline is not the same as an essential tremor.

Where are you seeing that harmaline accumulates in brain tissue over time? I cannot find this.

I know everyone is different, but myself and many others here have used harmalas daily for extended periods of time and to my knowledge none of us have developed Parkinson's disease as a result.

I think it's unlikely that your tremor is due to your frequent changa use over the summer. For me, I know that during times when I've been particularly anxious in my life I've developed a tremor that stayed around for a few weeks or months (until I felt better). There could be many other causes for it. If you are really worried about it, I'd say see a doctor.
 
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Thank you for the replies. What exactly is meant by inverse GABA-A agonism? Does this mean less GABA is reaching the receptor due to the beta carbolines? How is this countered and do you have a source regarding this mechanism?

I agree that what I've found online is confusing and rather contradictory - I'm not sure what to make of it.
 
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Its a bit more complicated than that apparently

Pharmacologic studies indicate that harmaline tremor severity is influenced by several glutamate receptors, GABA A and B receptors, serotonin receptors, norepinephrine receptors, dopamine receptors, gap junctions, T-type calcium channels, alcohol, and antiepileptic drugs.
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www.ncbi.nlm.nih.gov

Harmaline Tremor: Underlying Mechanisms in a Potential Animal Model of Essential Tremor

Harmaline and harmine are tremorigenic β-carbolines that, on administration to experimental animals, induce an acute postural and kinetic tremor of axial and truncal musculature. This drug-induced action tremor has been proposed as a model of ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Seems that they are indeed cytotoxic to a degree due to their structural similarity to MPTP and MPP

The low affinities of βCs at the DAT protein are most likely the rate-limiting factor for selective dopaminergic toxicity. Conclusively, high concentrations of and/or prolonged exposure to βC derivatives might be necessary to produce significant dopaminergic toxicity. This does not rule out the possible involvement of βC derivatives in the pathophysiology of PD since the slow progression of this disease suggests a mild and prolonged degenerative process.
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So this really does not bode well for me. From what I gather, I caused damage to the dopamine neurons and the effect is likely permanent (and could possibly lead to more serious issues down the road). That's really unfortunate and I'm shocked that this isn't being discussed elsewhere in the DMT community. It seems that discussion of harmala use should come with an explicit warning. As I said above I would have been a lot more cautious if this had been on my radar. :(
 
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From my experience, Harmalas aren't dangerous or toxic, and do not cause Dopaminergic damage lol. I've taken Peganum Harmala a lot since 2012, probably more than anyone else has i'd imagine lol, and have even taken strong/heavy Rue dosages daily/near daily with the reverse tolerance built up for the past 8 or so months, but stopped taking it a few days ago, i haven't noticed anything negative or toxic about it at all.

And i'm pretty certain the tremoring is caused by the GABA-A inverse agonism, and has only been noticeable to me in extremely heavy dosages. Lemon Balm seemed to work pretty well to clean up how the Rue feels, and to me it felt like it counteracted the GABA-A inverse agonism by inhibiting GABA Transaminase and raising GABA levels potentially counteracting the GABA-A inverse agonism. There's also Lemon EO which cleans the Rue up quite well. There's also things like Skullcap or Passion Flower, things which can bind to GABA-A subchannels as Positive Allosteric Modulators. But i do agree that Peganum Harmala and even B. Caapi, as well as DMT-containing plants should definitely be studied more thoroughly. There's also using a combination of Rue and Caapi, using Caapi to boost Harmine and THH levels while using Rue as the main source of MAO-A inhibition, like 3 grams or so of Rue seed with the rest being Caapi to help balance things out so that it's not so Harmaline-heavy.

With that said though, i think you're really over-thinking/exaggerating this, ime Harmalas have been really safe and i haven't noticed anything negative about them or Rue seed. I love my Rue seed, and would never trade it for Caapi. And if something like this were possible, that Rue caused some sort of toxicity in people, i'm pretty sure we'd be hearing/reading more about it.
 
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mmcakes said:
I smoked my fair share of changa over this past summer (quite a bit, most days) and I've had a persistent essential tremor that I've noticed since October.
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Whatever may be the situation with your tremors and whatever may be the cause, you should see a doctor if you think that your health is compromised. There could be many other causes for the tremors that you report. Ruling out in advance, and based on hearsay and fear, any other causes than the changa that you have been smoking could possibly mean overlooking signs of a serious medical complication. Please do consider having an independent investigation made by a qualified medical practitioner.

mmcakes said:
Apparently there is a causative link between harmaline consumption and this neurological issue, which is unfortunate (had I known this at the time I would probably not have smoked this). There is also a potential link to Parkinsons, which I really hope I don't get in the future. Apparently the beta carbolines (harmaline in particular) are fat soluble and accumulate in brain tissue.
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Can you quote citations for these claims? I mean citations proving a definite causative link, not mere hypothesizing and guesswork. I have been looking into these matters before and could not find such indications. To the contrary, I got the impression that a lot of highly tenuous inferences are made on the basis of a purported similarity with MPP+. Upon critical review, it is reported that these similarities do not hold out in actuality.

For more information and some citations, see this and this post that I wrote earlier. The latter post even presents an article indicating the neuroprotective effects of harmala alkaloids against MPP+ neurotoxicity.

For now, I'd say that, based on evidence obtained from scientific research, the harmala alkaloids are more likely to counteract than to cause Parkinson's disease. Attached at the end of this post is an article about harmine as a treatment for Parkinson's disease.

What remains unknown, however, is what exactly the effects of smoked harmala alkaloids are. We do not know very well what the possible products of pyrolysis are and what effects these may have.

mmcakes said:
I'm curious if any other harmala users (heavy users) have noted this occurrence and if anyone has identified a solution or a way to detoxify this chemicals from the brain.
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We should consider your report seriously. If anyone can confirm these effects that you describe, they should let us know. I cannot remember seeing any complaints like yours being reported here up until now. There were some isolated reports of nausea and vomiting after smoking changa, that's all that I am aware of. Perhaps you have an uncommon genetic trait that makes you susceptible to negative side effects that most others do not have.

mmcakes said:
It's really unfortunate that I have this now, even though it's relatively mild - I use my hands for work and play guitar etc. Even typing on my phone is fairly difficult and the tremors are exacerbated by various stressors which sometimes makes them unmanageable. I really hope to find a solution and want to warn others.
Click to expand...
Let's not panic. It's not clear what underlying condition you actually have. There is no positive and conclusive causative relation of harmalas to Parkinsosn's disease. As you say, other stressors apparently play a role. Please consult a doctor first before settling on a diagnosis. In the mean time, if other people can give more data points, that might be helpful.

--

Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson's Disease?
Atbin Djamshidian MD, PhD, Sabine Bernschneider-Reif PhD, Werner Poewe MD and Andrew J. Lees MD, FRCP
Movement Disorders Clinical Practice, Vol. 3, Issue 1, Jan/Feb 2016, pg. 19-26
doi: 10.1002/mdc3.12242

Abstract:
Banisteriopsis caapi, a liana indigenous to the Amazon basin with metagnomigenic properties and possible anti-depressant effects is one of the natural sources of harmala alkaloids. A summary of early trials with extracts of Banisteriopsis caapi and Peganum harmala (from which harmine was first isolated) in the 1920s and 1930s on various forms of parkinsonism is given as well as a brief overview of the known pharmacological properties of harmine. Despite its earlier abandonment because of perceived weaker efficacy than solanaceous alkaloids like scopolamine and hyoscine we propose that harmine should be reconsidered as a potential rapidly acting anti-Parkinsonian agent.
 

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Thank you again for the responses.

Pitubo, I read the links you posted, but I'm afraid my level of scientific understanding doesn't really provide me with much insight or conclusions that put my mind at ease.

The claim that harmaline (and harmane) are causatively linked to Essential Tremor and Parkinsons was a claim I read on the wikipedia page for essential tremor. The sources listed are:

link.springer.com

Elevated levels of harman and norharman in cerebrospinal fluid of Parkinsonian patients - Journal of Neural Transmission

Death of dopaminergic neurons in Parkinson's disease (PD) may partially be caused by synthesis and accumulation of endogenous and exogenous toxins. Because of structural similarity to MPTP, β-carbolines, like norharman and harman, have been proposed as putative neurotoxins. In vivo they may...
link.springer.com link.springer.com

- It seems to me that these references don't really support the claims on the wikipedia page for Essential Tremor (Essential tremor - Wikipedia), but again I'm not scientifically literate enough to draw conclusions either way.

- It seems that Harmane is established as neurotoxic and indicated in essential tremor and Parkinsons as well. I would think that given the chemical similarities between Harmane, Harmine, Harmaline and Tetraharmaline, it's reasonable to suspect each of these might present similar risks.

- I should note that these symptoms became apparent after a brief round of .25mg daily dose of quetiapine (Seroquel) that I took for about 20 days at the end of the summer. This medication is also implicated in causing ET and 'extrapyramidal' side effects, but I have my doubts as to this being the cause for a few reasons. One is that the dose is comparatively very small and the time frame very short - from what I've read on the subject, most people experience negative side effects after prolonged use and on much higher doses. However, I've considered that this use was on the tail end of the a summer of copious usage of inhaled harmalas. Perhaps the combination of the two affected my dopamine system in a negative way. I should also note that I noticed the symptoms some time after that course, but that doesn't mean that the symptoms weren't present before then. I'm also hesitant to bring this up because I honestly think the large doses of harmalas are more likely to be the culprit and don't want to provide a scapegoat in a forum where I'm sure there is some bias towards classifying harmalas as safe.

- The tremors are relatively mild in most situations and my initial awareness of them (and subsequent anxiety in regards to them) has made me ever cognizant of the potential health woes I've caused myself - this leads to my last point. This could be psychosomatic, though I have my doubts. My life circumstances changed around the time this whole ordeal started and while I don't find myself more stressed than normal, it's possible that my ruminating about the issue is causing the issue itself or at least exacerbating it. It's certainly the case that acute stress brings about its worst form. For instance, anxiety before and during interviewing for jobs makes the persistence and magnitude of the tremors significantly worse. The tremors also become minimized during more relaxed times, but do not seem to subside entirely. I should also note that I've found some minor relief over the past few days adopting a ketogenic diet, which some people have anecdotally claimed has helped significantly. There is still a fair amount of rigidity to my hand movements that worries me and my fingers quiver if I extend them in certain positions, but the dietary changes seem to have provided some positive change. I'm certainly the type of person to obsessively dwell on and worry about such physical ailments, so this whole ordeal has been scary and painful for me. I appreciate the responses and insight and do plan on seeing a doctor within the next few weeks. I'm happy to provide updates if people are interested.

Thanks again for the involved discussion.
 
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A few additional points:

- It interesting that you brought up the potential pyrolysis effects - it would be interesting to know what byproducts appear when smoking the harmala.

- One of my primary concerns is the apparent fat solubility of these various compounds. Given the amounts I've done, it's very concerning to me that significant concentrations of the harmine and harmaline might just be sitting around in my brain tissue permanently. Can anyone provide insight into how fat soluble these compounds really are and what methods might be employed to encourage metabolism and removal from the brain? (not that this will necessarily correct any damage to dopamine neurons that's already occurred)

- Also I will try the passion flower, lemon balm and skullcap to see if they make any difference. Can anyone elucidate how these compounds theoretically work to this end?
 
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